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Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis.

Sobral-Leite M, Wesseling J, Smit VT, Nevanlinna H, van Miltenburg MH, Sanders J, Hofland I, Blows FM, Coulson P, Patrycja G, Schellens JH, Fagerholm R, Heikkilä P, Aittomäki K, Blomqvist C, Provenzano E, Ali HR, Figueroa J, Sherman M, Lissowska J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Phillips KA, kConFab/AOCS InvestigatorsCouch FJ, Olson JE, Vachon C, Visscher D, Brenner H, Butterbach K, Arndt V, Holleczek B, Hooning MJ, Hollestelle A, Martens JW, van Deurzen CH, van de Water B, Broeks A, Chang-Claude J, Chenevix-Trench G, Easton DF, Pharoah PD, García-Closas M, de Graauw M, Schmidt MK - BMC Med (2015)

Bottom Line: ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age.ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. m.leite@nki.nl.

ABSTRACT

Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients.

Methods: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model.

Results: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).

Conclusions: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.

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ANXA1 expression profile. Percentage of patients with ANXA1 positive tumors according to breast cancer subtypes comparing BCAC (excluding 37 patients with BRCA1 or BRCA2 mutations) versus BRCA1/2 mutation carriers. For the subtype analysis, patients with missing information for ER, PR and/or HER2 were excluded (393 in BCAC and 36 in BRCA1/2 mutation carriers). Luminal 1 subtype was defined as ER+ and/or PR+ and HER2-, and triple negative (TN) was defined as ER-, PR- and HER2-. Numbers of HER2+ were too small in the BRCA1/2 mutation carriers to make a comparison. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; TN: Triple negative
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Fig1: ANXA1 expression profile. Percentage of patients with ANXA1 positive tumors according to breast cancer subtypes comparing BCAC (excluding 37 patients with BRCA1 or BRCA2 mutations) versus BRCA1/2 mutation carriers. For the subtype analysis, patients with missing information for ER, PR and/or HER2 were excluded (393 in BCAC and 36 in BRCA1/2 mutation carriers). Luminal 1 subtype was defined as ER+ and/or PR+ and HER2-, and triple negative (TN) was defined as ER-, PR- and HER2-. Numbers of HER2+ were too small in the BRCA1/2 mutation carriers to make a comparison. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; TN: Triple negative

Mentions: In the case of significant associations between ANXA1 expression and a histopathological variable as evaluated by the Chi-square test, the odds ratios (OR) and their respective 95 % confidence intervals (95 % CI) adjusted for independent clinical variables (ORadj) were assessed using logistic regression models. The ANXA1 expression was tested for linear-by-linear associations to calculate trend significances (Ptrend) between tumor subtypes in Fig. 1. The statistical association analyses were conducted using SPSS 20 (SPSS Inc., Chicago, IL, USA).Fig. 1


Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis.

Sobral-Leite M, Wesseling J, Smit VT, Nevanlinna H, van Miltenburg MH, Sanders J, Hofland I, Blows FM, Coulson P, Patrycja G, Schellens JH, Fagerholm R, Heikkilä P, Aittomäki K, Blomqvist C, Provenzano E, Ali HR, Figueroa J, Sherman M, Lissowska J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Phillips KA, kConFab/AOCS InvestigatorsCouch FJ, Olson JE, Vachon C, Visscher D, Brenner H, Butterbach K, Arndt V, Holleczek B, Hooning MJ, Hollestelle A, Martens JW, van Deurzen CH, van de Water B, Broeks A, Chang-Claude J, Chenevix-Trench G, Easton DF, Pharoah PD, García-Closas M, de Graauw M, Schmidt MK - BMC Med (2015)

ANXA1 expression profile. Percentage of patients with ANXA1 positive tumors according to breast cancer subtypes comparing BCAC (excluding 37 patients with BRCA1 or BRCA2 mutations) versus BRCA1/2 mutation carriers. For the subtype analysis, patients with missing information for ER, PR and/or HER2 were excluded (393 in BCAC and 36 in BRCA1/2 mutation carriers). Luminal 1 subtype was defined as ER+ and/or PR+ and HER2-, and triple negative (TN) was defined as ER-, PR- and HER2-. Numbers of HER2+ were too small in the BRCA1/2 mutation carriers to make a comparison. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; TN: Triple negative
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4489114&req=5

Fig1: ANXA1 expression profile. Percentage of patients with ANXA1 positive tumors according to breast cancer subtypes comparing BCAC (excluding 37 patients with BRCA1 or BRCA2 mutations) versus BRCA1/2 mutation carriers. For the subtype analysis, patients with missing information for ER, PR and/or HER2 were excluded (393 in BCAC and 36 in BRCA1/2 mutation carriers). Luminal 1 subtype was defined as ER+ and/or PR+ and HER2-, and triple negative (TN) was defined as ER-, PR- and HER2-. Numbers of HER2+ were too small in the BRCA1/2 mutation carriers to make a comparison. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; TN: Triple negative
Mentions: In the case of significant associations between ANXA1 expression and a histopathological variable as evaluated by the Chi-square test, the odds ratios (OR) and their respective 95 % confidence intervals (95 % CI) adjusted for independent clinical variables (ORadj) were assessed using logistic regression models. The ANXA1 expression was tested for linear-by-linear associations to calculate trend significances (Ptrend) between tumor subtypes in Fig. 1. The statistical association analyses were conducted using SPSS 20 (SPSS Inc., Chicago, IL, USA).Fig. 1

Bottom Line: ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age.ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. m.leite@nki.nl.

ABSTRACT

Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients.

Methods: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model.

Results: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).

Conclusions: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.

Show MeSH
Related in: MedlinePlus